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用于区分活动性肺结核与潜伏性结核感染的HLA-DR特异性细胞与结核抗原/植物血凝素比值的联合检测

Combination of HLA-DR on -Specific Cells and Tuberculosis Antigen/Phytohemagglutinin Ratio for Discriminating Active Tuberculosis From Latent Tuberculosis Infection.

作者信息

Luo Ying, Xue Ying, Tang Guoxing, Lin Qun, Song Huijuan, Liu Wei, Yin Botao, Huang Jin, Wei Wei, Mao Liyan, Wang Feng, Sun Ziyong

机构信息

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Immunol. 2021 Nov 11;12:761209. doi: 10.3389/fimmu.2021.761209. eCollection 2021.

Abstract

BACKGROUND

Novel approaches for tuberculosis (TB) diagnosis, especially for distinguishing active TB (ATB) from latent TB infection (LTBI), are urgently warranted. The present study aims to determine whether the combination of HLA-DR on (MTB)-specific cells and TB antigen/phytohemagglutinin (TBAg/PHA) ratio could facilitate MTB infection status discrimination.

METHODS

Between June 2020 and June 2021, participants with ATB and LTBI were recruited from Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort), respectively. The detection of HLA-DR on MTB-specific cells upon TB antigen stimulation and T-SPOT assay were simultaneously performed on all subjects.

RESULTS

A total of 116 (54 ATB and 62 LTBI) and another 84 (43 ATB and 41 LTBI) cases were respectively enrolled from Qiaokou cohort and Caidian cohort. Both HLA-DR on IFN-γTNF-α cells and TBAg/PHA ratio showed discriminatory value in distinguishing between ATB and LTBI. Receiver operator characteristic (ROC) curve analysis showed that HLA-DR on IFN-γTNF-α cells produced an area under the ROC curve (AUC) of 0.886. Besides, TBAg/PHA ratio yield an AUC of 0.736. Furthermore, the combination of these two indicators resulted in the accurate discrimination with an AUC of 0.937. When the threshold was set as 0.36, the diagnostic model could differentiate ATB from LTBI with a sensitivity of 92.00% and a specificity of 81.82%. The performance obtained in Qiaokou cohort was further validated in Caidian cohort.

CONCLUSIONS

The combination of HLA-DR on MTB-specific cells and TBAg/PHA ratio could serve as a robust tool to determine TB disease states.

摘要

背景

迫切需要用于结核病(TB)诊断的新方法,尤其是用于区分活动性结核病(ATB)和潜伏性结核感染(LTBI)。本研究旨在确定结核分枝杆菌(MTB)特异性细胞上的HLA-DR与结核抗原/植物血凝素(TBAg/PHA)比值的组合是否有助于鉴别MTB感染状态。

方法

2020年6月至2021年6月,分别从同济医院(硚口队列)和中法新城院区(蔡甸队列)招募了ATB和LTBI参与者。对所有受试者同时进行结核抗原刺激后MTB特异性细胞上HLA-DR的检测和T-SPOT检测。

结果

分别从硚口队列和蔡甸队列纳入了116例(54例ATB和62例LTBI)以及另外84例(43例ATB和41例LTBI)病例。IFN-γTNF-α细胞上的HLA-DR和TBAg/PHA比值在区分ATB和LTBI方面均显示出鉴别价值。受试者工作特征(ROC)曲线分析显示,IFN-γTNF-α细胞上的HLA-DR产生的ROC曲线下面积(AUC)为0.886。此外,TBAg/PHA比值的AUC为0.736。此外,这两个指标的组合导致准确鉴别,AUC为0.937。当阈值设定为0.36时,诊断模型区分ATB和LTBI的灵敏度为92.00%,特异性为81.82%。在硚口队列中获得的结果在蔡甸队列中得到进一步验证。

结论

MTB特异性细胞上的HLA-DR与TBAg/PHA比值的组合可作为确定结核病状态的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92be/8632229/9d5e65729dac/fimmu-12-761209-g001.jpg

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